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Alphavirus Pathogenesis and Immunity

  • Chapter
The Togaviridae and Flaviviridae

Part of the book series: The Viruses ((VIRS))

Abstract

Most alphavirus infections in nature occur in wild birds, rodents, and occasionally reptiles and amphibians. Some of these natural hosts sustain a relatively asymptomatic, prolonged, high-titered viremia, facilitating transmission of the virus by mosquitoes (Chamberlain, 1980). Although there is undoubtedly mortality and morbidity in the wild due to alphavirus infections, many native species have inapparent infection, and epizootic, epidemic, or endemic disease is usually recognized after mosquito-mediated transmission to a domestic host (e.g., horses, pigeons, captive pheasants) or to man. Affected individuals develop a wide range of symptoms, including fever, skin rashes, arthritis, myositis, and/or encephalitis. Depending on the virus and on the host, the infection may be clinically inapparent or cause fulminant disease and death (Shope, 1980).

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References

  • Aaskov, J. G., Davies, C. E. A., Tucker, M., and Dalglish, D., 1981a, Effect on mice of infection during pregnancy with three Australian arboviruses, Am. J. Trop. Med. Hyg. 30: 198–203.

    PubMed  CAS  Google Scholar 

  • Aaskov J. G. Mataika, J. U., Lawrence, G. W. Rabukawaga, V., Tucker, M.M. Miles, J. A. R., and Daglish, D. A. 1981b, An epidemic of Ross River virus infection in Fiji, 1979, Am. J. Trop. Med. Hyg. 30: 1053–1059.

    PubMed  CAS  Google Scholar 

  • Aaskov, J. G., Nair, K., Lawrence, G. W., Dalglish, D. A., and Tucker, M., 1981c, Evidence for transplacental transmission of Ross River virus in humans, Med. J. Aust. 2: 20–21.

    PubMed  CAS  Google Scholar 

  • Aaskov, J. G., Ross, P., Davies, C. E. A., Innis, M. D., Guard, R. W., Stallman, N. D., and Tucker, M., 1981d, Epidemic polyarthritis in northeastern Australia, 1978–1979, Med. J. Aust. 2: 17–19.

    PubMed  CAS  Google Scholar 

  • Aaskov, J. G., Hadding, U., and Bitter-Suermann, 1985, Interaction of Ross River virus with the complement system, J. Gen. Virol. 66: 121–129.

    Article  PubMed  CAS  Google Scholar 

  • Adler, W. H., and Rabinowitz, S. G., 1973, Host defenses during primary Venezuelan equine encephalomyelitis virus infection in mice. II. In vitro methods for the measurement and qualitation of the immune response, J. Immunol. 110: 1354–1362.

    PubMed  CAS  Google Scholar 

  • Aguilar, M. J., 1970, Pathological changes in brain and other target organs of infant and weanling mice after infection with non-neuroadapted Western equine encephalitis virus, Infect. Immun 2: 533–542.

    PubMed  CAS  Google Scholar 

  • Airhart, J. W., Trevino, G. S., and Craig, C. P., 1969, Alterations in immune responses by attenuated Venezuelan equine encephalitis vaccine. II. Pathology and soluble antigen localization in guinea pigs, J. Immunol. 102: 1228–1234.

    PubMed  CAS  Google Scholar 

  • Anders, E. M., Miller, J. F. A. P., and Gamble, J., 1979, A radioisotopic technique for measuring the mononuclear inflammatory response in Sindbis virus-induced encephalitis of mice, J. Immunol. Methods 29: 167–171.

    Article  PubMed  CAS  Google Scholar 

  • Anderson, S. G., Doherty, R. L., and Carley, J. G., 1961, Epidemic polyarthritis: Antibody to a group A arthropod-borne virus in Australia and the island of New Guinea, Med. J. Aust. 1: 273–276.

    Google Scholar 

  • Atkins, G. J., 1983, The avirulent A7 strain of Semliki Forest virus has reduced cytopathogenicity for neuroblastoma cells compared to the virulent L10 strain, J. Gen. Virol. 64: 1401–1404.

    Article  PubMed  CAS  Google Scholar 

  • Atkins, G. J., and Sheahan, B. J., 1982, Semliki Forest virus neurovirulence mutants have altered cytopathogenicity for central nervous system cells, Infect. Immun. 36: 333–341.

    PubMed  CAS  Google Scholar 

  • Atkins, G. J., Carter, J., and Sheahan, B. J., 1982, Effect of alphavirus infection on mouse embryos, Infect. Immun. 38: 1285–1290.

    PubMed  CAS  Google Scholar 

  • Austin, F. J., and Scherer, W. F., 1971, Studies of viral virulence. I. Growth and histopathology of virulent and attenuated strains of Venezuelan encephalitis virus in hamsters, Am. J. Pathol. 62: 195–209.

    PubMed  CAS  Google Scholar 

  • Bark, R. S., Trent, D. W., and Johnston, R. E., 1981, A Sindbis virus variant with a cell-determined latent period, Virology 110: 237–242.

    Article  Google Scholar 

  • Baron, S., and Buckler, C. E., 1963, Circulating interferon in mice after intravenous injection of virus, Science 144: 1061–1063.

    Article  Google Scholar 

  • Barrett, A. D. T., and Dimmock, N. J., 1984a, Modulation of a systemic Semliki Forest virus infection in mice by defective interfering virus, J. Gen. Virol. 65: 1827–1831.

    Article  PubMed  Google Scholar 

  • Barrett, A. D. T., and Dimmock, N. J., 1984b, Properties of host and virus which influence defective interfering virus mediated-protection of mice against Semliki Forest virus lethal encephalitis, Arch. Virol. 81: 185–188.

    Article  PubMed  CAS  Google Scholar 

  • Barrett, P. N., Sheahan, B. J., and Atkins, G. J., 1980, Isolation and preliminary characterization of Semliki Forest virus mutants with altered virulence, J. Gen. Virol. 49: 141–147.

    Article  PubMed  CAS  Google Scholar 

  • Bastian, F. O., Wende, R. D., Singer, D. B., and Zeller, R. S., 1975, Eastern equine encephalomyelitis: Histopathologic and ultrastructural changes with isolation of the virus in a human case, Am. J. Clin. Pathol. 64: 10–13.

    PubMed  CAS  Google Scholar 

  • Bell, J. R., Kinney, R. M., Trent, D. W., Strauss, E. G., and Strauss, J. H., 1984, An evolutionary tree relating eight alphaviruses, based on amino-terminal sequences of their glycoproteins, Proc. Natl. Acad. Sci. U.S.A. 81: 4702–4706.

    Article  PubMed  CAS  Google Scholar 

  • Berge, T. O., Gleiser, C. A., Gochenour, W. S., Jr., Miesse, M. L., and Tigertt, W. P., 1961, Studies on the virus of Venezuelan equine encephalomyelitis. II. Modification by specific immune serum of response of central nervous system of mice, J. Immunol. 87: 509–517.

    PubMed  CAS  Google Scholar 

  • Berger, M. L., 1980, Humoral and cell-mediated immune mechanisms in the production of pathology in virulent Semliki Forest virus encephalitis, Infect. Immun. 30: 244–253.

    PubMed  CAS  Google Scholar 

  • Blackman, M. J., and Morris, A. G., 1984, Gamma interferon production and cytotoxicity of spleen cells from mice infected with Semliki Forest virus. J. Gen. Virol. 65: 955–961.

    Article  PubMed  CAS  Google Scholar 

  • Boere, W. A. M., Benaissa-Trouw, B. J., Harmsen, M., Kraaijeveld, C. A., and Snippe, H., 1983, Neutralizing and non-neutralizing monoclonal antibodies to the E2 glycoprotein of Semliki Forest virus can protect mice from lethal encephalitis, J. Gen. Virol. 64: 1405–1408.

    Article  PubMed  CAS  Google Scholar 

  • Boere, W. A. M., Harmsen, T., Vinje, J., Benaissa-Trouw, B. J., Kraaijeveld, C. A., and Snippe, H., 1984, Identification of distinct antigenic determinants on Semliki Forest virus by using monoclonal antibodies with different antiviral activities, J. Virol. 52: 575–582.

    PubMed  CAS  Google Scholar 

  • Boone, L. R., and Brown, A., 1976, Variants of the HR strain of Sindbis virus lethal for mice, J. Gen. Virol. 31: 261–263.

    Article  PubMed  CAS  Google Scholar 

  • Bradish, C. J., and Allner, K., 1972, The early responses of mice to respiratory or intraperitoneal infection by defined virulent and avirulent strains of Semliki Forest virus, J. Gen. Virol. 15: 205–218.

    Article  PubMed  CAS  Google Scholar 

  • Bradish, C. J., and Titmuss, D., 1981, The effects of interferon and double-stranded RNA upon the virus—host interaction: Studies with togavirus strains in mice, J. Gen. Virol. 53: 21–30.

    Article  PubMed  CAS  Google Scholar 

  • Bradish, C. J., Allner, K., and Maber, H. B., 1971, The virulence of original and derived strains of Semliki Forest virus for mice, guinea pigs and rabbits, J. Gen. Virol. 12: 141–160.

    Article  PubMed  CAS  Google Scholar 

  • Bradish, C. J., Allner, K., and Fitzgeorge, R., 1975, Immunomodification and the expression of virulence in mice by defined strains of Semliki Forest virus: The effects of cyclophosphamide, J. Gen. Virol. 28: 225–237.

    Article  PubMed  CAS  Google Scholar 

  • Bradish, C. J., Fitzgeorge, R., Titmuss, D., and Baskerville, A., 1979, The responses of nudeathymic mice to nominally avirulent togavirus infections, J. Gen. Virol. 42: 555–566.

    Article  PubMed  CAS  Google Scholar 

  • Brown, A., and Officer, J. E., 1975, An attenuated variant of Eastern encephalitis virus: Biological properties and protection induced in mice, Arch. Virol. 47: 123–138.

    Article  PubMed  CAS  Google Scholar 

  • Brown, A., Vosdingh, R., and Zebovitz, E., 1975, Attenuation and immunogenicity of is mutants of Eastern encephalitis virus for mice, J. Gen. Virol. 27: 111–116.

    Article  PubMed  CAS  Google Scholar 

  • Burns, W. H., Billups, L. C., and Notkins, A. L., 1975, Thymus dependence of viral antigens, Nature London 256: 654–655.

    Article  PubMed  CAS  Google Scholar 

  • Carey, D. E., Myers, R. M., DeRainitz, C. M., Jadhav, M., and Reuben, R., 1969, The 1964 Chikungunya epidemic at Vellore, South India, including observations on concurrent dengue, Trans. R. Soc. Trop. Med. Hyg. 63: 434–445.

    Article  PubMed  CAS  Google Scholar 

  • Carreras, B., Griffin, D. E., and Silverstein, A. M., 1982, Sindbis virus-induced ocular immunopathology, Invest. Ophthalmol. Vis. Sci. 22: 571–578.

    PubMed  CAS  Google Scholar 

  • Casals, J., 1963, Relationships among arthropod-borne animal viruses determined by cross-challenge tests, Am. J. Trop. Med. Hyg. 12: 587–596.

    PubMed  CAS  Google Scholar 

  • Chamberlain, R. W., 1980, Epidemiology of arthropod-borne togarviruses: The role of arthropods as hosts and vectors and of vertebrate hosts in natural transmission cycles, in: The Togaviruses: Biology, Structure, Replication ( R. W. Schlesinger, ed.), pp. 175–227, Academic Press, New York.

    Google Scholar 

  • Chamberlain, R. W., Kissling, R. E., Stamm, D. D., Nelson, D. B., and Sikes, R. K., 1956, Venezuelan equine encephalomyelitis in wild birds, Am. J. Hyg. 63: 261–273.

    PubMed  CAS  Google Scholar 

  • Chanas, A. C., Gould, E. A., Clegg, J. C. S., and Varma, M. G. R., 1982, Monoclonal antibodies to Sindbis virus glycoprotein E1 can neutralize, enhance infectivity, and independently inhibit haemagglutination or haemolysis, J. Gen. Virol. 58: 37–46.

    Article  PubMed  CAS  Google Scholar 

  • Chew-Lim, M., 1975, Mouse encephalitis induced by avirulent Semliki Forest virus, Vet. Pathol. 12: 387–393.

    PubMed  CAS  Google Scholar 

  • Chew-Lim, M., 1979, Brain viral persistence and myelin damage in nude mice, Can. J. Comp. Med. 43: 39–43.

    PubMed  CAS  Google Scholar 

  • Chew-Lim, M., Suckling, A J., and Webb, H. E., 1977a, Demyelination in mice after two or three infections with avirulent Semliki Forest virus, Vet. Pathol. 14: 67–72.

    Article  Google Scholar 

  • Chew-Lim, M., Webb, H. E., and Jagelman, S., 1977b, The effect of irradiation on demyelination induced by avirulent Semliki Forest virus, Br. J. Exp. Pathol. 58: 459–464.

    PubMed  CAS  Google Scholar 

  • Cole, F. E., Jr., and McKinney, R. W., 1971, Cross-protection in hamsters immunized with group A arbovirus vaccines, Infect. Immun. 4: 37–41.

    PubMed  Google Scholar 

  • Copps, S. C., and Giddings, L. E., 1959, Transplacental transmission of Western equine encephalitis: Report of a case, Pediatrics 24: 31–33.

    PubMed  CAS  Google Scholar 

  • Craig, C. P., Reynolds, S. L., Airhart, J. W., and Staab, E. V., 1969, Alterations in immune responses by attenuated Venezuelan equine encephalitis vaccine. I. Adjuvant effect of VEE virus infection in guinea pigs, J. Immunol. 102: 1220–1227.

    PubMed  CAS  Google Scholar 

  • Cremer, N. E., Lennette, E. H., Hagens, S. J., and Fujimoto, F. Y., 1966, Difference in mechanism of viral neutralization under in vitro and in vivo conditions, J. Immunol. 96: 284–288.

    PubMed  CAS  Google Scholar 

  • Crouch, C. F., Mackenzie, A., and Dimmock, N. J., 1982, The effect of defective-interfering Semliki Forest virus on the histopathology of infection with virulent Semliki Forest virus in mice, J. Infect. Dis. 146: 411–416.

    Article  PubMed  CAS  Google Scholar 

  • Dal Canto, M. C., and Rabinowitz, S. G., 1981, Central nervous system demyelination in Venezuelan equine encephalomyelitis infection: An experimental model of virus-induced myelin injury, J. Neurol. Sci. 49: 397–418.

    Article  Google Scholar 

  • Dalrymple, J. M., Schlesinger, S., and Russell, P. K., 1976, Antigenic characterization of two Sindbis envelope glycoproteins separated by isoelectric focusing, Virology 69: 93–103.

    Article  PubMed  CAS  Google Scholar 

  • Danes, L., Kutner, J., Hruskova, J., and Rychterova, V., 1973, The role of the olfactory route on infection of the respiratory tract with Venezuelan equine encephalomyelitis virus in normal and operated Macaca rhesus monkeys. I. Results of virological examination, Acta Virol. 17: 50–56.

    PubMed  CAS  Google Scholar 

  • Davis, W. A., 1940, Study of birds and mosquitoes as hosts for virus of Western equine encephalomyelitis, Am. J. Hyg. Sect. C 32: 45–59.

    Google Scholar 

  • Dill, G. S., Pederson, C. E., and Stookey, J. L., 1973, A comparison of the tissue lesions produced in adult hamsters by two strains of avirulent Venezuelan equine encephalomyelitis virus, Am. J. Pathol. 72: 13–24.

    PubMed  Google Scholar 

  • Dimmock, N. J., and Kennedy, S. T., 1978, Prevention of death in Semliki Forest virus-infected mice by administration of defective interfering Semliki Forest virus, J. Gen. Virol. 39: 231–242.

    Article  PubMed  CAS  Google Scholar 

  • Doby, P. B., Schnurrenberger, P. R., Martin, R. J., Hanson, L. E., Sherrick, G. W., and Schoenholz, W. K., 1966, Western encephalitis in Illinois horses and ponies, J. Am. Vet. Med. Assoc. 148: 422–427.

    PubMed  CAS  Google Scholar 

  • Doherty, P. C., 1973, Quantitative studies of the inflammatory process in fatal viral meningoencephalitis, Am. J. Pathol. 73: 607–622.

    PubMed  CAS  Google Scholar 

  • Doherty, P. C., 1984, Clearance of experimental viral infections of the central nervous system, in: Serono Symposia, Vol. 12, Neuroimmunology ( P. O. Behan and F. Spreafico, eds.), pp. 301–310, Raven Press, New York.

    Google Scholar 

  • Doherty, R. L., 1977, Arthropod-borne viruses in Australia, Aust. J. Exp. Biol. Med. Sci. 55: 103–130.

    Article  PubMed  CAS  Google Scholar 

  • Doherty, R. L., Anderson, S. G., Aaron, K., Farnworth, J. K., Knyvett, A. F., and Nimmo, D., 1961, Clinical manifestations of infection with group A arthropod-borne viruses in Queensland, Med. J. Aust. 1: 276–279.

    Google Scholar 

  • Doherty, R. L., Gorman, B. M., Whitehead, R. H., and Carley, J. G., 1964, Studies of epidemic polyarthritis: The significance of three group-A arboviruses isolated from mosquitoes in Queensland, Aust. Ann. Med. 13: 322–327.

    PubMed  CAS  Google Scholar 

  • Doherty, R. L., Bodey, A. S., and Carew, J. S., 1969, Sindbis virus infection in Australia, Med. J. Aust. 2: 1016–1017.

    PubMed  CAS  Google Scholar 

  • Dremov, D. P., Solyanik, R. G., Miryutova, T. L., and Laptokova, L. M., 1978, Attenuated variants of Eastern equine encephalomyelitis virus: Pathomorphological, immunofluorescence and virological studies of infection in Syrian hamsters, Acta Virol. 22: 139–145.

    PubMed  CAS  Google Scholar 

  • Earnest, M. P., Goolishian, H. A., Calverley, J. R., Hayes, R. O., and Hill, H. R., 1971, Neurologic, intellectual and psychologic sequelae following western encephalitis: A follow-up of 35 cases, Neurology 21: 969–974.

    Article  PubMed  CAS  Google Scholar 

  • Ehrenkranz, N. J., and Ventura, A. K., 1974, Venezuelan equine encephalitis virus infection in man, Annu. Rev. Med. 25: 9–14.

    Article  PubMed  CAS  Google Scholar 

  • Eisner, R. J., and Nusbaum, S. R., 1983, Encephalitis vaccination of pheasants: A question of efficacy, J. Am. Vet. Med. Assoc. 183: 280–281.

    PubMed  CAS  Google Scholar 

  • Emini, E. A., and Wiebe, M. E., 1981, An attenuated mutant of Venezuelan encephalitis virus: Biochemical alterations and their genetic association with attenuation, Virology 110: 185–196.

    Article  PubMed  CAS  Google Scholar 

  • Espmark, A., and Niklasson, B., 1984, Ockelbo disease in Sweden: Epidemiological, clinical and virological data from the 1982 outbreak, Am. J. Trop. Med. Hyg. 33: 1203–1211.

    PubMed  CAS  Google Scholar 

  • Farber, S., Hill, A., Connerly, M. L., and Dingle, J. H., 1940, Encephalitis in infants and children caused by the virus of the Eastern variety of equine encephalitis, J. Am. Med. Assoc. 114: 1725–1731.

    Article  Google Scholar 

  • Fazakerley, J. K., Amor, S., and Webb, H. E., 1983, Reconstitution of Semliki Forest virus infected mice induces immune mediated pathological changes in the CNS, Clin. Exp. Immunol. 52: 115–120.

    PubMed  CAS  Google Scholar 

  • Fearon, D. T., 1979, Activation of the alternative complement pathway, Crit. Rev. Immunol. 1: 1–32.

    CAS  Google Scholar 

  • Feemster, R. F., 1957, Equine encephalitis in Massachusetts, N. Engl. J. Med. 257: 701–704.

    Article  PubMed  CAS  Google Scholar 

  • Finley, K. H., Longshore, W. A., Palmer, R. J., Cook, R. E., and Riggs, N., 1955, Western equine and St. Louis encephalitis: Preliminary report of a clinical followup study in California, Neurology 5: 223–235.

    Article  PubMed  CAS  Google Scholar 

  • Finter, N. B., 1966, Interferon as an antiviral agent in vivo: Quantitative and temporal respects of the protection of mice against Semliki Forest virus, Br. J. Exp. Pathol. 47: 361–369.

    PubMed  CAS  Google Scholar 

  • Fothergill, L. D., and Dingle, J. H., 1938, Fatal disease of pigeons caused by the virus of the Eastern variety of equine encephalitis, Science 88: 549–550.

    Article  PubMed  CAS  Google Scholar 

  • France, J. K., Wyrick, B. C., and Trent, D. W., 1979, Biochemical and antigenic comparisons of the envelope glycoproteins of Venezuelan equine encephalomyelitis strains, J. Gen. Virol. 44: 725–740.

    Article  PubMed  CAS  Google Scholar 

  • Garcia-Tamayo, J., 1973, Venezuelan equine encephalomyelitis virus in the heart of newborn mice, Arch. Pathol. 96: 294–297.

    PubMed  CAS  Google Scholar 

  • Garcia-Tamayo, J., Carreno, G., and Esparza, J., 1979, Central nervous system alterations in sequelae of Venezuelan equine encephalitis virus infection in the rat, J. Pathol. 128: 87–91.

    Article  PubMed  CAS  Google Scholar 

  • Garcia-Tamayo, J., Esparza, J., and Martinez, J., 1981, Placental and fetal alterations due to Venezuelan equine encephalitis virus in rats, Infect Immun. 32: 813–821.

    PubMed  CAS  Google Scholar 

  • Gates, M. D., Brown, A., and Wust, C. J., 1982, Comparison of specific and cross reactive antigens of alphaviruses on virions and infected cells, Infect. Immun. 35: 248–255.

    PubMed  CAS  Google Scholar 

  • Gates, C., Sheahan, B. J., and Atkins, G. J., 1984, The pathogenicity of the M9 mutant of Semliki Forest virus in immunocompromised mice, J. Gen. Virol. 65: 73–80.

    Article  PubMed  Google Scholar 

  • Gidlund, M., Orn, A., Wigzell, H., Senik, A., and Gresser, I., 1978, Enhanced NK cell activity in mice injected with interferon and interferon inducers, Nature Londonl 273: 759–761.

    Article  CAS  Google Scholar 

  • Gilden, D. H., Cole, G. A., and Nathanson, N., 1972, Immunopathogenesis of acute central nervous system disease produced by lymphocytic choriomeningitis virus. II. Adoptive immunization of virus carriers, J. Exp. Med. 135: 874–889.

    Article  PubMed  CAS  Google Scholar 

  • Glasgow, L. A., 1966, Leukocytes and interferon in the host response to viral infections. II. Enhanced interferon response of leukocytes from immune animals, J. Bacteriol. 91: 2185–2191.

    PubMed  CAS  Google Scholar 

  • Gleiser, C. A., Cochenour, W. S., Berge, T. O., and Tigertt, W. D., 1962, The comparative pathology of experimental Venezuelan equine encephalomyelitis infection in different animal hosts, J. Infect. Dis. 110: 80–97.

    Article  PubMed  CAS  Google Scholar 

  • Goldfield, M., Welsh, J. N., and Taylor, B. F., 1968, The 1959 outbreak of Eastern encephalitis in New Jersey. 5. The inapparent infection:disease ratio, Am. J. Epidemiol. 87: 32–38.

    PubMed  CAS  Google Scholar 

  • Gorelkin, L., 1973, Venezuelan equine encephalomyelitis in an adult animal host: An electron microscopy study, Am. J. Pathol. 73: 425–434.

    PubMed  CAS  Google Scholar 

  • Gorelkin, L., and Jahrling, P. B., 1974, Pancreatic involvement by Venezuelan equine encephalomyelitis virus in the hamster, Am. J. Pathol. 75: 349–362.

    PubMed  CAS  Google Scholar 

  • Gorelkin, L., and Jahrling, P. B., 1975, Virus-initiated septic shock: Acute death of Venezuelan encephalitis virus-infected hamsters, Lab. Invest. 32: 78–85.

    PubMed  CAS  Google Scholar 

  • Grayson, M. A., and Galindo, P., 1968, Epidemiologic studies of Venezuelan equine encephalitis virus in Almirante, Panama, Am. J. Epidemiol. 88: 80–96.

    PubMed  CAS  Google Scholar 

  • Griffin, D. E., 1976, Role of the immune response in age-dependent resistance of mice to encephalitis due to Sindbis virus, J. Infect. Dis. 133: 456–464.

    Article  PubMed  CAS  Google Scholar 

  • Griffin, D. E., 1981, Immunoglobulins in the cerebrospinal fluid: Changes during acute viral encephalitis in mice, J. Immunol. 126: 27–31.

    PubMed  CAS  Google Scholar 

  • Griffin, D. E., 1984, The inflammatory response to acute viral infections, in: Concepts in Viral Pathogenesis ( A. L. Notkins and M. B. A. Oldstone, eds.), pp. 46–52, Springer-Verlag, New York.

    Chapter  Google Scholar 

  • Griffin, D. E., and Hess, J. L., 1986, Cells with natural killer activity in the CSF of normal and athymic nude mice with acute Sindbis virus encephalitis J. Immunol. (in press).

    Google Scholar 

  • Griffin, D. E., and Johnson, R. T., 1973, Cellular immune response to viral infection: In vitro studies of lymphocytes from mice infected with Sindbis virus, Cell. Immunol. 9: 426–434.

    Article  PubMed  CAS  Google Scholar 

  • Griffin, D. E., and Johnson, R. T., 1977, Role of the immune response in recovery from Sindbis virus encephalitis in mice, J. Immunol. 118: 1070–1075.

    PubMed  CAS  Google Scholar 

  • Griffin, D. E., Mokhtarian, F., Park, M. M., and Hirsch, R. L., 1983, Immune responses to acute alphavirus infection of the central nervous system: Sindbis virus encephalitis in mice, in: Progress in Brain Research, Vol. 59, Immunology of Nervous System Infections ( P. O. Behan, V. ter Meulen, and F. C. Rose, eds.), pp. 11–21, Elsevier, New York.

    Google Scholar 

  • Grimley, P. M., and Friedman, R. M., 1970, Arboviral infection of voluntary striated muscles, J. Infect. Dis. 122: 45–52.

    Article  PubMed  CAS  Google Scholar 

  • Guard, R. W., McAuliffe, M. J., Stallman, N. D., and Bramston, B. A., 1982, Haemorrhagic manifestations with Sindbis virus: Case report, Pathology 14: 89–90.

    Article  PubMed  CAS  Google Scholar 

  • Hackbarth, S. A., Reinerz, A. B. G., and Sagik, B. P., 1973, Age-dependent resistance of mice to Sindbis virus infection: Reticuloendothelial role, J. Reticuloendothel. Soc. 14: 405–425.

    PubMed  CAS  Google Scholar 

  • Haddow, A. J., Davies, C. W., and Walker, A. J., 1960, O’nyong-nyong fever: An epidemic virus disease in East Africa. I. Introduction, Trans. R. Soc. Trop. Med. Hyg. 54: 517–522.

    Article  Google Scholar 

  • Hart, K. L., Keen, D., and Belle, E. A., 1964, An outbreak of Eastern equine encephalomyelitis in Jamaica, West Indies. I. Description of human cases, Am. J. Trop. Med. 13: 331–334.

    CAS  Google Scholar 

  • Hearn, H. J., Jr., 1960, A variant of Venezuelan equine encephalomyelitis virus attenuated for mice and monkeys, J. Immunol. 84: 626–629.

    PubMed  Google Scholar 

  • Hearn, H. J., and Rainey, C. T., 1963, Cross-protection in animals infected with group A arbovirus, J. Immunol. 90: 720–724.

    PubMed  Google Scholar 

  • Helenius, A., Fries, E., Garoff, H., and Simons, K., 1976, Solubilization of the Semliki Forest virus membrane with sodium deoxycholate, Biochim. Biophys. Acta 436: 319–334.

    Article  PubMed  CAS  Google Scholar 

  • Henderson, B. E., Chappel, W. A., Johnston, J. G., Jr., and Sudia, W. D., 1971, Experimental infection of horses with three strains of Venezuelan equine encephalitis virus. I. Clinical and virological studies, Am. J. Epidemiol. 93: 194–205.

    PubMed  CAS  Google Scholar 

  • Herberman, R. B., and Holden, H. T., 1978, Natural cell-mediated cytotoxicity, Adv. Cancer Res. 27: 305–377.

    Article  PubMed  CAS  Google Scholar 

  • Hirsch, R. L., 1981, Natural killer cells appear to play no role in the recovery of mice from Sindbis virus infection, Immunology 43: 81–89.

    PubMed  CAS  Google Scholar 

  • Hirsch, R. L., 1982, The complement system: Its importance in the host response to viral infection, Microbiol. Rev. 46: 71–85.

    PubMed  CAS  Google Scholar 

  • Hirsch, R. L., and Griffin, D. E., 1979, The pathogenesis of Sindbis virus infection in athymic nude mice, J. Immunol. 123: 1215–1218.

    PubMed  CAS  Google Scholar 

  • Hirsch, R. L., Griffin, D. E., and Winkelstein, J. A., 1978, The effect of complement depletion on the course of Sindbis virus infection in mice, J. Immunol. 121: 1276–1278.

    PubMed  CAS  Google Scholar 

  • Hirsch, R. L., Griffin, D. E., and Johnson, R. T., 1979, Interactions between immune cells and antibody in protection from fatal Sindbis virus encephalitis, Infect. Immun. 23: 320–324.

    PubMed  CAS  Google Scholar 

  • Hirsch, R. L., Griffin, D. E., and Winkelstein, J. A., 1980a, The role of complement in viral infections. IV. The participation of the terminal complement components (C5–9) in recovery of mice from Sindbis virus infection, Infect. Immun. 30: 899–901.

    PubMed  CAS  Google Scholar 

  • Hirsch, R. L., Winkelstein, J. A., and Griffin, D. E., 1980b, The role of complement in viral infections. III. Activation of the classical and alternative pathways by Sindbis virus, J. Immunol. 124: 2507–2510.

    PubMed  CAS  Google Scholar 

  • Hirsch, R. L., Griffin, D. E., and Winkelstein, J. A., 1981, Host modification of Sindbis virus sialic acid content influences alternative complement pathway activation and virus clearance, J. Immunol. 127: 1740–1743.

    PubMed  CAS  Google Scholar 

  • Hirsch, R. L., Griffin, D. E., and Winkelstein, J. A., 1983, Natural immunity to Sindbis virus is influenced by host tissue sialic acid content, Proc. Natl. Acad. Sci. U.S.A. 80: 548–550.

    Article  PubMed  CAS  Google Scholar 

  • Howard, R. J., Craig, C. P., Trevino, G. S., Dougherty, S. F., and Mergenhagen, S. E., 1969, Enhanced humoral immunity in mice infected with attenuated Venezuelan equine encephalitis virus, J. Immunol. 103: 699–707.

    PubMed  CAS  Google Scholar 

  • Howitt, B. F., 1932, Equine encephalomyelitis, J. Infect. Dis. 51: 493–510.

    Google Scholar 

  • Hruskova, J., Rychterova, V., and Kliment, V., 1972, The influence of infection with Venezuelan equine encephalomyelitis virus on antibody response against sheep erythrocytes. I. Experiments on mice, Acta. Virol. 16: 115–124.

    PubMed  CAS  Google Scholar 

  • Hsieh, P., Rosner, M. R., and Robbins, P. W., 1983, Host-dependent variation of asparagine-linked oligosaccharides at individual glycosylation sites of Sindbis virus glycoproteins, J. Biol. Chem. 258: 2548–2554.

    PubMed  CAS  Google Scholar 

  • Hunt, A. R., and Roehrig, J. T., 1985, Biochemical and biological characteristics of epitopes on the El glycoprotein of Western equine encephalitis virus, Virology 142: 334–346.

    Article  PubMed  CAS  Google Scholar 

  • Igarashi, A., Fukuoka, T., and Fukai, K., 1971, Passive immunization of mice with rabbit antisera against Chikungunya virus and its components, Biken J. 14: 353–355.

    PubMed  CAS  Google Scholar 

  • Illavia, S. J., Webb, H. E., and Pathak, S., 1982, Demyelination induced in mice by avirulent Semliki Forest virus. I. Virology and effects on optic nerve, Neuropathol. Appl. Neurobiol. 8: 35–42.

    Article  PubMed  CAS  Google Scholar 

  • Jagelman, S., Suckling, A. J., Webb, H. E., and Bowen, E. T. W., 1978, The pathogenesis of avirulent Semliki Forest virus infections in athymic nude mice, J. Gen. Virol. 41: 599–607.

    Article  PubMed  CAS  Google Scholar 

  • Jahrling, P. B., and Scherer, W. F., 1973a, Histopathology and distribution of viral antigens in hamsters infected with virulent and benign Venezuelan encephalitis viruses, Am. J. Pathol. 72: 25–38.

    PubMed  CAS  Google Scholar 

  • Jahrling, P. B., and Scherer, W. F., 1973b, Growth curves and clearance rates of virulent and benign Venezuelan encephalitis viruses in hamsters, Infect. Immun. 8: 456–462.

    PubMed  CAS  Google Scholar 

  • Jahrling, P. B., Dindy, E., and Eddy, G. A., 1974, Correlates to increased lethality of attenuated Venezuelan encephalitis virus vaccine for immunosuppressed hamsters, Infect. Immun 9. 924–930.

    PubMed  CAS  Google Scholar 

  • Jahrling, P. B., Hilmas, D. E., and Heard, C. D., 1977, Vascular clearance of Venezuelan equine encephalomyelitis viruses as a correlate to virulence for rhesus monkeys, Arch. Virol. 55: 161–164.

    Article  PubMed  CAS  Google Scholar 

  • Jahrling, P. B., DePaoli, A., and Powanda, M. C., 1978, Pathogenesis of a Venezuelan encephalitis virus strain lethal for adult white rats, J. Med. Virol. 2: 109–116.

    Article  PubMed  CAS  Google Scholar 

  • Jahrling, P. B., Hesse, R. A., Anderson, A. O., and Gangemi, J. D., 1983, Opsonization of alphaviruses in hamsters, J. Med. Virol. 12: 1–16.

    Article  PubMed  CAS  Google Scholar 

  • Johnson, E. D., and Cole, G. A., 1975, Functional heterogeneity of lymphocytic choriomeningitis virus-specific T lymphocytes. I. Identification of effector and memory subsets, J. Exp. Med. 141: 8–66.

    Google Scholar 

  • Johnson, H. N., 1963, Selection of a variant of Western encephalitis virus of low pathogenicity for study as a live virus vaccine, Am. J. Trop. Med. Hyg. 12: 604–610.

    Google Scholar 

  • Johnson, K. M., Shelokov, A., Peralta, P. H., Dammin, G. J., and Young, N. A., 1968, Recovery of Venezuelan equine encephalomyelitis virus in Panama, Am. J. Trop. Med. Hyg. 17: 432–440.

    PubMed  CAS  Google Scholar 

  • Johnson, R. T., 1965, Virus invasion of the central nervous system: A study of Sindbis virus infection in the mouse using fluorescent antibody, Am. J. Pathol. 46: 929–943.

    PubMed  CAS  Google Scholar 

  • Johnson, R. T., 1966, The incubation period of viral encephalitis, NINDB Monogr. 2, Slow, Latent and Temperate Virus Infections, National Institute of Neurological Diseases and Blindness Monogr. 2 (D. C. Gajdusek, C. J. Gibbs, and M. Alpers, eds.), U. S. Govt. Printing Office, Washington, D. C., pp. 119–124.

    Google Scholar 

  • Johnson, R. T., 1971, Inflammatory response to viral infection, in: Immunological Dis- orders of the Nervous System, Res. Publ. Assoc. Res. Nerv. Ment. Dis. 69: 305–312.

    Google Scholar 

  • Johnson, R. T., McFarland, H. F., and Levy, S. E., 1972, Age-dependent resistance to viral encephalitis: Studies of infections due to Sindbis virus in mice, J. Infect. Dis. 125: 257–262.

    Article  PubMed  CAS  Google Scholar 

  • Jungherr, E. L., Helmboldt, C. F., Satriano, S. F., and Luginbuhl, R. E., 1957, Investigation of Eastern equine encephalomyelitis. III. Pathology in pheasants and incidental observations in feral birds, Am. J. Hyg. 67: 10–20.

    Google Scholar 

  • Kaluza, G., Rott, R., and Schwarz, R. T., 1980, Carbohydrate-induced conformational changes of Semliki Forest virus glycoproteins determine antigenicity, Virology 102: 286–299.

    Article  PubMed  CAS  Google Scholar 

  • Keegstra, K., and Burke, D., 1977, Comparison of the carbohydrate of Sindbis virus glycoprotein with the carbohydrate of host glycoproteins, J. Supramol. Struct. 7: 371–379.

    Article  PubMed  CAS  Google Scholar 

  • Kennedy, A. C., Fleming, J., and Solomon, L., 1980, Chikungunya viral arthropathy: A clinical description, J. Rheumatol. 7: 231–236.

    PubMed  CAS  Google Scholar 

  • King, B., Wust, C. J., and Brown, A., 1977, Antibody-dependent complement mediated homologous and cross cytolysis of togavirus-infected cells, J. Immunol. 119: 1289–1292.

    PubMed  CAS  Google Scholar 

  • Kissling, R. E., Chamberlain, R. W., Sikes, R. K., and Eidson, M. E., 1954a, Studies on the North American arthropod-borne encephalitides. III. Eastern equine encephalitis in wild birds, Am. J. Hyg. 60: 251–265.

    PubMed  CAS  Google Scholar 

  • Kissling, R. E., Eidson, M. E., and Stamm, D. D., 1954b, Transfer of maternal neutralizing antibodies against Eastern equine encephalomyelitis virus in birds, J. Infect. Dis. 95: 179–181.

    Article  PubMed  CAS  Google Scholar 

  • Kissling, R. E., Chamberlain, R. W., Nelson, D. B., and Stamm, D. D., 1956, Venezuelan equine encephalomyelitis in horses, Am. J. Hyg. 63: 274–287.

    PubMed  CAS  Google Scholar 

  • Kokernot, R. H., Shinefield, H. R., and Longshore, W. A., 1953, The 1952 outbreak of encephalitis in California, Calif. Med. 79: 73–77.

    PubMed  CAS  Google Scholar 

  • Kraaijeveld, C. A., Harmsen, M., and Boutahar-Trouw, B. K., 1979a, Cellular immunity against Semliki Forest virus in mice, Infect. Immun. 23: 213–218.

    PubMed  CAS  Google Scholar 

  • Kraaijeveld, C. A., Harmsen, M., and Boutahar-Trouw, B. K., 1979b, Delayed type hypersensitivity against Semliki Forest virus in mice, Infect. Immun. 23: 219–223.

    PubMed  CAS  Google Scholar 

  • Krieger, J. N., Scherer, W. F., Wiebe, M. E., Pancake, B. A., and Harsayi, Z. P., 1979, A hamster-attenuated, temperature-sensitive mutant of Venezuelan encephalitis virus, Infect. Immun. 25: 873–879.

    PubMed  CAS  Google Scholar 

  • Kundin, W. D., Liu, C., and Rodina, P., 1966, Pathogenesis of Venezuelan equine encephalomyelitis virus. I. Infection in suckling mice, J. Immunol. 96: 39–48.

    PubMed  CAS  Google Scholar 

  • Lagwinska, E., Stewart, C. C., Adles, C., and Schlesinger, S., 1975, Replication of lactic dehydrogenase virus and Sindbis virus in mouse peritoneal macrophages: Induction of interferon and phenotypic mixing, Virology 65: 204–214.

    Article  PubMed  CAS  Google Scholar 

  • Latif, Z., Gates, D., Wust, C. J., and Brown, A., 1979, Cross protection among togaviruses in nude mice and littermates, J. Gen. Virol. 45: 89–98.

    Article  PubMed  CAS  Google Scholar 

  • LeBlanc, P. A., Scherer, W. F., and Susdorf, D. H., 1978, Infections of congenitally athymic (nude) and normal mice with avirulent and virulent strains of Venezuelan encephalitis virus, Infect. Immun. 21: 779–785.

    PubMed  CAS  Google Scholar 

  • Lennette, E. H., and Koprowski, H., 1943, Human infection with Venezuelan equine encephalomyelitis virus: A report on eight cases of infection acquired in the laboratory, J. Am. Med. Assoc. 123: 1088–1095.

    Article  Google Scholar 

  • Lennette, E. H., and Koprowski, H., 1944, Influence of age on the susceptibility of mice to infection with certain neurotropic viruses, J. Immunol. 49: 175–191.

    Google Scholar 

  • Leon, C. A., Jaramillo, R., Martinez, S., Fernandez, F., Tellez, H., Lasso, B., and de Guzman, R., 1975, Sequelae of Venezuelan equine encephalitis in humans: A four year follow-up, Int. J. Epidemiol. 4: 131–140.

    Article  PubMed  CAS  Google Scholar 

  • Levitt, N. H., Miller, H. V., and Edelman, R., 1979, Interaction of alphaviruses with human peripheral leukocytes: In vitro replication of Venezuelan equine encephalomyelitis virus in monocyte cultures, Infect. Immun. 24: 642–646.

    PubMed  CAS  Google Scholar 

  • Liu, C., Voth, D. W., Rodina, P., Shauf, L. R., and Gonzalez, G., 1970, A comparative study of the pathogenesis of Western equine and Eastern equine encephalomyelitis viral infections in mice by intracerebral and subcutaneous inoculations, J. Infect. Dis. 122: 53–63.

    Article  PubMed  CAS  Google Scholar 

  • London, W. T., Levitt, N. H., Kent, S. G., Wong, V. G., and Sever, J. L., 1977, Congenital cerebral and ocular malformations induced in rhesus monkeys by Venezuelan equine encephalitis virus, Teratology 16: 285–296.

    Article  PubMed  CAS  Google Scholar 

  • Longshore, W. A., Stevens, I. M., Hollister, A. C., Gittelsohn, A., and Lennette, E. H., 1956, Epidemiologic observations on acute infectious encephalitis in California, with special reference to the 1952 outbreak, Am. J. Hyg. 63: 69–86.

    PubMed  Google Scholar 

  • Macfarlan, R. I., Burns, W. H., and White, D. O., 1977, Two cytotoxic cells in the peritoneal cavity of virus-infected mice: Antibody-dependent macrophages and non-specific killer cells, J. Immunol. 119: 1569–1574.

    PubMed  CAS  Google Scholar 

  • Mackenzie, A., Suckling, A. J., Jagelman, S., and Wilson, A. M., 1978, Histopathological and enzyme histochemical changes in experimental Semliki Forest virus infection in mice and their relevance to scrapie, J. Comp. Pathol. 88: 335–344.

    Article  PubMed  CAS  Google Scholar 

  • Malherbe, H., Strickland-Cholmley, M., and Jackson, A. L., 1963, Sindbis virus infection in man: Report of a case with recovery of virus from skin lesions, S. Afr. Med. j. 37: 547–552.

    CAS  Google Scholar 

  • Marker, S. C., and Ascher, M. S., 1976, Specific in vitro lymphocyte transformation with Venezuelan equine encephalitis virus, Cell. Immunol. 23: 32–38.

    Article  PubMed  CAS  Google Scholar 

  • Mathews, J. H., and Roehrig, J. T., 1982, Determination of the protective epitopes on the glycoproteins of Venezuelan equine encephalomyelitis virus by passive transfer of monoclonal antibodies, J. Immunol. 129: 2763–2767.

    PubMed  CAS  Google Scholar 

  • Mayer, V., Ibrahim, A. H., and Gajdosova, E., 1973, Viral infection and resistance in immunosuppressed host. III. Intracerebral challenge with Sindbis virus in immunized or interferon inducer given mice, Acta Virol. 17: 29–40.

    PubMed  CAS  Google Scholar 

  • McFarland, H. F., 1974, In vitro studies of cell-mediated immunity in an acute viral infection, J. Immunol. 113: 173–180.

    CAS  Google Scholar 

  • McFarland, H. F., Griffin, D. E., and Johnson, R. L., 1972, Specificity of the inflammatory response in viral encephalitis. I. Adoptive immunization of immunosuppressed mice infected with Sindbis virus, J. Exp. Med. 136: 216–226.

    Article  PubMed  CAS  Google Scholar 

  • McIntosh, D. M., McGillivrary, G. M., Dickinson, D. B., and Malherbe, H., 1964, Illness caused by Sindbis and West Nile viruses in South Africa, S. Afr. Med. J. 38: 291–294.

    PubMed  CAS  Google Scholar 

  • Mecham, J. O., and Trent, D. W., 1982, Glycosylation patterns of the envelope glycoproteins of an equine-virulent Venezuelan encephalitis virus and its vaccine derivative, J. Gen. Virol. 63: 121–129.

    Article  PubMed  CAS  Google Scholar 

  • Mecham, J. O., and Trent, D. W., 1983, A biochemical comparison of the in vitro replication of a virulent and an avirulent strain of Venezuelan encephalitis virus, J. Gen. Virol. 64: 1111–1119.

    Article  PubMed  CAS  Google Scholar 

  • Milner, A. R., and Marshall, I. D., 1984, Pathogenesis of in utero infections with abortigenic and non-abortigenic alphaviruses in mice, J. Virol. 50: 66–72.

    PubMed  CAS  Google Scholar 

  • Milner, A. R., Marshall, I. D., and Mullbacher, A., 1984, Effect of pregnancy on stimulation of alphavirus immunity in mice, J. Virol. 50: 73–76.

    PubMed  CAS  Google Scholar 

  • Mims, C. A., Murphy, F. A., Taylor, W. P., and Marshall, I. D., 1973, Pathogenesis of Ross River virus infection in mice. I. Ependymal infection, cortical thinning, and hydrocephalus, J. Infect. Dis. 127: 121–128.

    Article  PubMed  CAS  Google Scholar 

  • Moench, T. R., and Griffin, D. E., 1984, Immunocytochemical identification and quantitation of mononuclear cells in cerebrospinal fluid, meninges, and brain during acute viral encephalitis, J. Exp. Med. 159: 77–88.

    Article  PubMed  CAS  Google Scholar 

  • Mohktarian, F., and Griffin, D. E., 1984, Role of mast cells in virus-induced CNS inflammation in the mouse, Cell. Immunol. 86: 491–500.

    Article  Google Scholar 

  • Mokhtarian, F., Griffin, D. E., and Hirsch, R. L., 1982, Production of mononuclear chemo- tactic factors during Sindbis virus infection in mice, Infect. Immun 35: 965–973.

    PubMed  CAS  Google Scholar 

  • Monath, T. P., Calisher, C. H., Davis, M., Bowen, G. S., and White, J., 1974, Experimental studies of rhesus monkeys infected with epizootic and enzootic subtypes of Venezuelan equine encephalitis virus, J. Infect. Dis. 129: 194–200.

    Article  PubMed  CAS  Google Scholar 

  • Monath, T. P., Kemp, G. E., Cropp, C. B., and Chandler, F. W., 1978, Necrotizing myocarditis in mice infected with Western equine encephalitis virus: Clinical, electrocardiographic, and histopathologic correlations, J. Infect. Dis. 138: 59–66.

    Article  PubMed  CAS  Google Scholar 

  • Morein, B., Barz, D., Koszinowski, U., and Schirrmacher, V., 1979, Integration of a virus membrane protein into the lipid bilayer of target cells as a prerequisite for immune cytolysis, J. Exp. Med. 150: 1383–1398.

    Article  PubMed  CAS  Google Scholar 

  • Morgan, I. M., 1941, Influence of age on susceptibility and on immune response of mice to Eastern equine encephalomyelitis virus, J. Exp. Med. 74: 115–132.

    Article  PubMed  CAS  Google Scholar 

  • Morgan, I. M., Schlesinger, R. W., and Olitsky, P. K., 1942, Induced resistance of the central nervous system to experimental infection with equine encephalomyelitis virus. I. Neutralizing antibody in the central nervous system in relation to cerebral resistance, J. Exp. Med. 76: 357–369.

    Article  PubMed  CAS  Google Scholar 

  • Mullbacher, A., Marshall, I. D., and Blanden, R. V., 1979, Crossreactive cytotoxic T cells to alphavirus infection, Scand. J. Immunol. 10: 291–296.

    Article  PubMed  CAS  Google Scholar 

  • Murphy, F. A., and Whitfield, S. G., 1970, Eastern equine encephalitis virus infection: Electron microscopic studies of mouse central nervous system, Exp. Mol. Pathol. 13: 131–146.

    Article  PubMed  CAS  Google Scholar 

  • Murphy, F. A., Harrison, A. K., and Collin, W. K., 1970, The role of extra-neural arbovirus infection in the pathogenesis of encephalitis: An electron microscopic study of Semliki Forest virus infection in mice, Lab. Invest. 22: 318–328.

    PubMed  CAS  Google Scholar 

  • Murphy, F. A., Taylor, W. P., Mims, C. A., and Marshall, I. D., 1973, Pathogenesis of Ross River virus infection in mice. II. Muscle, heart and brown fat lesions, J. Infect. Dis. 127: 129–138.

    Article  PubMed  CAS  Google Scholar 

  • Niklasson, B., Espmark, A., LeDuck, J. W., Gargan, T. P., Ennis, W. A., Tesh, R. B., and Main, A. J., Jr., 1984, Association of a Sindbis-like virus with Ockelbo disease in Sweden, Am. J. Trop. Med. Hyg. 33: 1212–1217.

    PubMed  CAS  Google Scholar 

  • Noran, H. H., and Baker, A. B., 1945, Western equine encephalitis: The pathogenesis of the pathological lesions, J. Neuropathol. Exp. Neuro 1 . 4: 269–276.

    Article  Google Scholar 

  • Nydegger, U. E., Fearon, D. T., and Austen, K. F., 1978, Autosomal locus regulates inverse relationship between sialic content and capacity of mouse erythrocytes to activate human alternative complement pathway, Proc. Natl. Acad. Sci. U.S.A. 75: 6078–6083.

    Article  PubMed  CAS  Google Scholar 

  • Oldstone, M. B. A., 1984, Virus-induced immune complex formation and disease: Definition, regulation, importance, in: Concepts in Viral Pathogenesis ( A. L. Notkins and M. B. A. Oldstone, eds.), pp. 201–209, Springer-Verlag, New York.

    Chapter  Google Scholar 

  • Olitsky, P. K., Schlesinger, R. W., and Morgan, I. M., 1943, Induced resistance of the central nervous system to experimental infection with equine encephalomyelitis virus. II. Serotherapy in Western virus infection, J. Exp. Med. 77: 359–375.

    Article  PubMed  CAS  Google Scholar 

  • Olmsted, R. A., Boric, R. S., Sawyer, B. A., and Johnston, R. E., 1984, Sindbis virus mutants selected for rapid growth in cell culture display attenuated virulence in animals, Science 225: 424–426.

    Article  PubMed  CAS  Google Scholar 

  • Oppenheim, J. J., 1981, Lymphokines, in: Cellular Functions in Immunity and Inflammation ( J. J. Oppenheim, D. L. Rosenstreich and M. Potter, eds.), pp. 259–282, Elsevier, New York.

    Google Scholar 

  • Park, M. M., Griffin, D. E., and Johnson, R. T., 1980, Analysis of the role of immune responses in recovery from acute Sindbis virus encephalitis: Studies in adult thymectomized lethally irradiated mice, Infect. Immun 34: 306–309.

    Google Scholar 

  • Parsons, L. M., and Webb, H. E., 1982, Virus titres and persistently raised white cell counts in cerebrospinal fluid in mice after peripheral infection with demyelinating Semliki Forest virus, Neuropathol. Appl. Neurobiol. 8: 395–401.

    Article  PubMed  CAS  Google Scholar 

  • Pathak, S., and Webb, H. E., 1974, Possible mechanisms for the transport of Semliki Forest virus into and within mouse brain: An electron microscopic study, J. Neurol. Sci. 23: 175–184.

    Article  PubMed  CAS  Google Scholar 

  • Peck, R., Brown, A., and Wust, C. J., 1979, In vitro heterologous cytotoxicity by T effector cells from mice immunized with Sindbis virus, J. Immunol. 123: 1763–1766.

    CAS  Google Scholar 

  • Pedersen, C. E., Jr., Slocum, D. R., and Eddy, G. A., 1973, Immunological studies on the envelope component of Venezuelan equine encephalomyelitis virus, Infect. Immun. 8: 901–906.

    PubMed  CAS  Google Scholar 

  • Pedersen, C. E., Jr., and Eddy, G. A., 1974, Separation, isolation, and immunological studies of the structural proteins of Venezuelan equine encephalomyelitis virus, J. Viral. 14: 740–744.

    CAS  Google Scholar 

  • Postic, B., Schleupner, C. J., Armstrong, J. A., and Ho, M., 1969, Two variants of Sindbis virus which differ in interferon induction and serum clearance. I. The phenomenon, J. Infect. Dis. 120: 339–347.

    Article  PubMed  CAS  Google Scholar 

  • Pruslin, F. H., and Rodman, T. C., 1978, Venezuelan encephalitis virus: In vivo induction of a chromosomal abnormality in hamster bone marrow cells, Infect. Immun. 19: 1104–1106.

    PubMed  CAS  Google Scholar 

  • Pusztai, R., Gould, E. A., and Smith, H., 1971, Infection patterns in mice of an avinaient and virulent strain of Semliki Forest virus, Br. J. Exp. Pathol. 52: 669–677.

    PubMed  CAS  Google Scholar 

  • Rabinowitz, S. G., 1976, Host immune responses after administration of inactivated Venezuelan equine encephalomyelitis virus vaccines. II. Kinetics of neutralizing antibody responses in donors and adoptively immunized recipients, J. Infect. Dis. 134: 39–47.

    Article  PubMed  CAS  Google Scholar 

  • Rabinowitz, S. G., and Adler, W. H., 1973, Host defenses during primary Venezuelan equine encephalomyelitis virus infection in mice. I. Passive transfer of protection with immune serum and immune cells, J. Immunol. 110: 1345–1353.

    PubMed  CAS  Google Scholar 

  • Rabinowitz, S. G., and Proctor, R. A., 1974, In vitro study of antiviral activity of immune spleen cells in experimental Venezuelan equine encephalomyelitis infection in mice, J. Immunol. 112: 1070–1077.

    PubMed  CAS  Google Scholar 

  • Rager-Zisman, B., and Bloom, B. R., 1982, Natural killer cells in resistance to virus-infected cells, Springer Semin. Immunopathol. 4: 397–414.

    Article  PubMed  CAS  Google Scholar 

  • Reeves, W. C., and Hammon, W., Mc.D., 1962, Epidemiology of the Arthropod-Borne Viral Encephalitides in Kern County, California, 1943–1952, University of California Publications in Public Health, Vol. 4, University of California Press, Berkeley.

    Google Scholar 

  • Reinarz, A. B. G., Broome, M. G., and Sagik, B. P., 1971, Age-dependent resistance of mice to Sindbis virus infection: Viral replication as a function of host age, Infect. Immun. 3: 268–273.

    PubMed  CAS  Google Scholar 

  • Robinson, M. C., 1955, An epidemic of virus disease in Southern province, Tanganyika Territory, in 1952–1953. I. Clinical features, Trans. R. Soc. Trop. Med. Hyg. 49: 28–32.

    Article  PubMed  CAS  Google Scholar 

  • Rodda, S. J., and White, D. O., 1976, Cytotoxic macrophages: A rapid nonspecific response to viral infection, J. Immunol. 117: 2067–2072.

    PubMed  CAS  Google Scholar 

  • Roehrig, J. T., Day, J. W., and Kinney, R. M., 1982, Antigenic analysis of the surface glycoproteins of a Venezuelan equine encephalitis virus (TC-83) using monoclonal antibodies, Virology 118: 269–278.

    Article  PubMed  CAS  Google Scholar 

  • Rosen, L., Gubler, D. J., and Bennett, P. H., 1981, Epidemic polyarthritis (Ross River) virus infection in the Cook Islands, Am. J. Trop. Med. Hyg. 30: 1294–1302.

    PubMed  CAS  Google Scholar 

  • Satriano, S. F., Luginbuhl, R. E., Wallis, R. C., Jungherr, E. L., and Williamson, L. A., 1957, Investigation of Eastern equine encephalomyelitis. IV. Susceptibility and transmission studies with virus of pheasant origin, Am. J. Hyg. 67: 21–34.

    Google Scholar 

  • Scherer, W. F., and Chin, J., 1977, Responses of guinea pigs to infections with strains of Venezuelan encephalitis virus, and correlations with equine virulence, Am. J. Trop. Med. Hyg. 26: 307–312.

    PubMed  CAS  Google Scholar 

  • Scherer, W. F., Ellsworth, C. A., and Ventura, A. K., 1971, Studies of viral virulence. II. Growth and adsorption curves of virulent and attenuated strains of Venezuelan encephalitis virus in cultured cells, Am. J. Pathol. 62: 211–219.

    PubMed  CAS  Google Scholar 

  • Scherer, W. F., Campillo-Sainz, C, Mucha-Macias, J. de, Dickerman, R. W., Wong Chia, C., and Zarate, M. L., 1972, Ecologic studies of Venezuelan encephalitis virus in Southeastern Mexico. VII. Infection of man, Am. J. Trop. Med. Hyg. 21: 79–85.

    PubMed  CAS  Google Scholar 

  • Schlesinger, R. W., 1949, The mechanism of active cerebral immunity to equine encephalomyelitis virus. II. The local antigenic booster effect of the challenge inoculum, J. Exp. Med. 89: 507–527.

    Article  PubMed  CAS  Google Scholar 

  • Schlesinger, R. W., Olitsky, P. K., Morgan, I. M., 1944, Induced resistance of the central nervous system to experimental infection with equine encephalomyelitis virus. III. Abortive infection with Western virus and subsequent interference with the action of heterologous virus, J. Exp. Med. 80: 197–211.

    Article  PubMed  CAS  Google Scholar 

  • Schleupner, C. J., Postic, B., Armstrong, J. A., Atchison, R. W., and Ho, M., 1969, Two variants of Sindbis virus which differ in interferon induction and serum clearance. II. Virological characterization, J. Infect. Dis. 120: 348–355.

    Article  PubMed  CAS  Google Scholar 

  • Schmaljohn, A. L., Johnson, E. D., Dalrymple, J. M., and Cole, G. A., 1982, Non-neutralizing monoclonal antibodies can prevent lethal aphavirus encephalitis, Nature (London) 297: 70–72.

    Article  CAS  Google Scholar 

  • Schmaljohn, A. L., Kokubun, K. M., and Cole, G. A., 1983, Protective monoclonal antibodies define maturational and pH-dependent antigenic changes in Sindbis virus El glycoprotein, Virology 130: 144–154.

    Article  PubMed  CAS  Google Scholar 

  • Seamer, J. H., Boulter, E. A., and Zlotnick, I., 1971, Delayed onset of encephalitis in mice passively immunized against Semliki Forest Virus, Br. J. Exp. Pathol. 52: 408–414.

    PubMed  CAS  Google Scholar 

  • Seay, A. R., and Wolinsky, J. S., 1982, Ross River virus-induced demyelination. I. Pathogenesis and histopathology, Ann. Neurol. 12: 380–389.

    Article  PubMed  CAS  Google Scholar 

  • Seay, A. R., Griffin, D. E., and Johnson, R. T., 1981, Experimental viral polymyositis: Age dependency and immune response to Ross River virus infection in mice, Neurology 31: 656–661.

    Article  PubMed  CAS  Google Scholar 

  • Sheahan, B. J., Barrett, P. N., and Atkins, G. J., 1981, Demyelination in mice resulting from infection with a mutant of Semliki Forest virus, Acta Neuropathol. 53: 129–136.

    Article  PubMed  CAS  Google Scholar 

  • Shinefield, M. R., and Townsend, T. E., 1953, Transplacental transmission of western equine encephalitis, J. Pediatr. 43: 21–25.

    Article  PubMed  CAS  Google Scholar 

  • Shope, R. E., 1980, Medical significance of togaviruses: An overview of diseases caused by togaviruses in man and in domestic and wild vertebrate animals, in: The Toga vi ruses: Biology, Structure and Replication ( R. W. Schlesinger, ed.), pp. 47–82, Academic Press, New York.

    Google Scholar 

  • Shope, R. E., 1985, Alphavirus diseases, in: Virology ( B. N. Fields, ed.), pp. 931–953, Raven Press, New York.

    Google Scholar 

  • Shore, H., 1961, O’nyong-yong fever: An epidemic virus disease in East Africa. I. Some clinical and epidemiological observations in the Northern province of Uganda, Trans. R. Soc. Trop. Med. Hyg. 55: 361–373.

    Article  Google Scholar 

  • Sissons, J. G. P., Schreiber, R. D., Cooper, N. R., and Oldstone, M. B. A., 1982, The role of antibody and complement in lysing virus-infected cells, Med. Microbiol. Immunol. 170: 221–227.

    Article  PubMed  CAS  Google Scholar 

  • Smillie, J., Pusztai, R., and Smith, H., 1973, Studies of the influence of host defence mechanisms on infection of mice with an avirulent or virulent strain of Semliki Forest virus, Br. J. Exp. Pathol. 54: 260–266.

    PubMed  CAS  Google Scholar 

  • Smith, C., Wolcott, J. A., Wust, C. J., and Brown, A., 1985, Detection of immunologically cross-reacting capsid protein of alphaviruses on the surfaces of infected L929 cells, J. Virol. 53: 198–204.

    PubMed  CAS  Google Scholar 

  • Spertzel, R. O., Crabbs, C. L., and Vaughn, R. E., 1972, Transplacental transmission of Venezuelan equine encephalomyelitis virus in mice, Infect. Immun. 6: 339–343.

    PubMed  CAS  Google Scholar 

  • Spiegelberg, H. L., 1974, Biological activities of immunoglobulins of different classes and subclasses, Adv. Immunol. 19: 259–294.

    Article  PubMed  CAS  Google Scholar 

  • Staab, E. V., Normann, S. J., and Craig, C. P., 1970, Alterations in reticuloendothelial function by infection with attenuated Venezuelan equine encephalitis (VEE) virus, J. Reticuloendothel. Soc. 8: 342–348.

    PubMed  CAS  Google Scholar 

  • Stanley, J., Cooper, S. J., and Griffin, D. E., 1985, Alphavirus neurovirulence: Monoclonal antibodies discriminating wild-type from neuroadapted Sindbis virus, J. Virol. 56: 110–119.

    PubMed  CAS  Google Scholar 

  • Stanley, J., Cooper, S. J., and Griffin, D. E., 1986, Monoclonal antibodies can protect and promote recovery from fatal Sindbis virus encephalitis J. Virol. (in press).

    Google Scholar 

  • Stollar, V., 1975, Immune lysis of Sindbis virus, Virology 66: 620–624.

    Article  PubMed  CAS  Google Scholar 

  • Stollar, V., Stollar, U. D., Kou, R., Harrap, K. A., and Schlesinger, R. W., 1976, Sialic acid content of Sindbis virus from vertebrate and mosquito cells: Equivalence of biological and immunological viral properties, Virology 69: 104.

    Article  PubMed  CAS  Google Scholar 

  • Suckling, A. J., Webb, H. E., Chew-Lim, M., and Oaten, S. W., 1976, Effect of an inapparent viral encephalitis on the levels of lysosomal glycosidases in mouse brain, J. Neurol. Sci. 29: 109–116.

    Article  PubMed  CAS  Google Scholar 

  • Suckling, A. J., Jagelman, S., and Webb, H. E., 1977, Brain lysosomal glycosidase activity in immunosuppressed mice infected with avirulent Semliki Forest virus, Infect. Immun 15: 386–391.

    PubMed  CAS  Google Scholar 

  • Suckling, A. J., Jagelman, S., and Webb, H. E., 1978a, A comparison of brain lysosomal enzyme activities in four experimental togavirus encephalitides, J. Neurol. Sci. 35: 355–364.

    Article  PubMed  CAS  Google Scholar 

  • Suckling, A. J., Pathak, S., Jagelman, S., and Webb, H. E., 1978b, Virus-associated demyelination: A model using avirulent Semliki Forest virus infection of mice, J. Neurol. Sci. 39: 147–154.

    Article  PubMed  CAS  Google Scholar 

  • Sudia, W. D., and Newhouse, V. F., 1975, Epidemic Venezuelan equine encephalitis in North America: A summary of virus—vector—host relationships, Am. j. Epidemiol. 101: 1–13.

    PubMed  CAS  Google Scholar 

  • Sudia, W. D., Newhouse, V. F., and Henderson, B. E., 1971, Experimental infections of horses with three strains of Venezuelan equine encephalomyelitis virus. II. Experimental vector studies, Am. J. Epidemiol. 93: 206–211.

    PubMed  CAS  Google Scholar 

  • Sussman, O., Cohen, D., Gerende, J. E., and Kissling, R. E., 1958, Equine encephalitis vaccine studies in pheasants under epizootic and pre-epizootic conditions, Ann. N. Y. Acad. Sci. 70: 328–341.

    Article  PubMed  CAS  Google Scholar 

  • Symington, J., McCann, A. K., and Schlesinger, M. J., 1977, Infectious virus—antibody complexes of Sindbis virus, Infect. Immun. 15: 720–725.

    PubMed  CAS  Google Scholar 

  • Tasker, J. B., Miesse, M. L., and Berge, T. O., 1962, Studies on the virus of Venezuelan equine encephalomyelitis. III. Distribution in tissues of experimentally infected mice, Am. J. Trop. Med. Hyg. 11: 844–850.

    PubMed  CAS  Google Scholar 

  • Taylor, R. M., Hurlbut, H. S., Work, T. H., Kingsbury, J. R., and Frothingham, T. E., 1955, Sindbis virus: A newly recognized arthropod-transmitted virus, Am. J. Trop. Med. Hyg. 4: 844–846.

    PubMed  CAS  Google Scholar 

  • Tazulakhova, E. B., Novakhatsky, A. S., and Yershov, F. I., 1973, Interferon induction by, and antiviral effect of poly (rI(-poly (rC) in experimental viral infection, Acta Virol. 17: 487–492.

    PubMed  CAS  Google Scholar 

  • Tesh, R. B., McLean, R. G., Shroyer, D. A., Calisher, C. H., and Rosen, L., 1981, Ross River virus (Togaviridae: Alphavirus(infection (epidemic polyarthritis) in American Samoa, Trans. R. Soc. Trop. Med. Hyg. 75: 426–431.

    Article  PubMed  CAS  Google Scholar 

  • Thind, I. S., and Price, W. H., 1969, The effect of cyclophosphamide treatment on experimental arbovirus infections, Am. J. Epidemiol. 90: 62–68.

    PubMed  CAS  Google Scholar 

  • Thiruvengadam, K. V., Kalyanasundaram, V., and Rajgopal, J., 1965, Clinical and pathological studies on Chikungunya fever in Madras City, Ind. J. Med. Res. 53: 729–744.

    CAS  Google Scholar 

  • Tyzzer, E. E., and Sellards, A. W., 1941, Pathology of equine encephalomyelitis in young chickens, Am. J. Hyg. Sect. B 33: 69–81.

    Google Scholar 

  • Victor, J., Smith, D. G., and Pollack, A. D., 1956, The comparative pathology of Venezuelan equine encephalomyelitis, J. Infect. Dis. 98: 55–66.

    Article  PubMed  CAS  Google Scholar 

  • Vilcek, J., 1964, Production of interferon by newborn and adult mice infected with Sindbis virus, Virology 22: 651–652.

    Article  PubMed  CAS  Google Scholar 

  • Walder, R., and Bradish, C. J., 1975, Venezuelan equine encephalomyelitis virus (VEEV): Strain differentiation and specification of virulence markers, J. Gen. Virol. 26: 265–275.

    Article  PubMed  CAS  Google Scholar 

  • Walker, D. H., Harrison, A., Murphy, K., Flemister, M., and Murphy, F. A., 1976, Lymphoreticular and myeloid pathogenesis of Venezuelan equine encephalitis in hamsters, Am. J. Pathol. 84: 351–370.

    PubMed  CAS  Google Scholar 

  • Weinbren, M. P., Kokernut, R. H., and Smithburn, K. C., 1956, Strains of Sindbis like virus isolated from culicene mosquitoes in the Union of South Africa. I. Isolation and properties, S. Afr. Med. J. 30: 631–636.

    PubMed  CAS  Google Scholar 

  • Wenger, F., 1977, Venezuelan equine encephalitis, Teratology 16: 359–362.

    Article  PubMed  CAS  Google Scholar 

  • Willems, W. R., Kaluza, G., Boschek, C. B., Barrier, H., Hager, H., Schutz, H. J., and Feistner, H., 1979, Semliki Forest virus: Cause of a fatal case of human encephalitis, Science 203: 1127–1129.

    Article  PubMed  CAS  Google Scholar 

  • Williams, M. C., and Woodall, J. P., 1961, O’nyong-nyong fever: An epidemic virus disease in East Africa. II. Isolation and some properties of the virus, Trans. R. Soc. Trop. Med. Hyg. 55: 135–141.

    Article  PubMed  CAS  Google Scholar 

  • Wolcott, J. A., Gates, D. W., Wust, C. J., and Brown, A., 1982a, Cross reactive, cell associated antigen on L929 cells infected with temperature sensitive mutants of Sindbis virus, Infect. Immun. 36: 704–709.

    PubMed  CAS  Google Scholar 

  • Wolcott, J. A., Wust, C. J., and Brown, A., 1982b, Immunization with one alphavirus cross primes cellular and humoral immune responses to a second alphavirus, J. Immunol. 129: 1267–1271.

    PubMed  CAS  Google Scholar 

  • Wolcott, J. A., Wust, C. J., and Brown, A., 1984, Identification of immunologically cross-reactive proteins of Sindbis virus: Evidence for unique conformation for El glycoprotein from infected cells, J. Virol. 49: 379–385.

    PubMed  CAS  Google Scholar 

  • Woodman, D. R., McManus, A. T., and Eddy, G. A., 1975, Extension of mean time to death of mice with a lethal infection of Venezuelan equine encephalomyelitis virus by antihymocyte serum treatment, Infect. Immun. 12: 1006–1011.

    PubMed  CAS  Google Scholar 

  • Worthington, M., and Baron, S., 1971, Late therapy with an interferon stimulator in an arbovirus encephalitis in mice, Proc. Soc. Exp. Biol. Med. 136: 323–327.

    PubMed  CAS  Google Scholar 

  • Wyckoff, R. W. G., and Tesar, W. C., 1939, Equine encephalomyelitis in monkeys, J. Immonol. 37: 329–343.

    Google Scholar 

  • Zichis, J., and Shaughnessy, H. J., 1940, Experimental Western equine encephalomyelitis: Successful treatment with hyperimmune rabbit serum, J. Am. Med. Assoc. 115: 1071–1078.

    Article  Google Scholar 

  • Zichis, J., and Shaughnessy, H. J., 1945, Successful treatment of experimental Western equine encephalomyelitis with hyperimmune rabbit serum, Am. J. Public Health. 35: 815–823.

    Article  CAS  Google Scholar 

  • Zlotnick, I., and Harris, W. J., 1970, The changes in cell organelles of neurons in the brains of adult mice and hamsters during Semliki Forest virus and Louping ill encephalitis, Br. J. Exp. Pathol. 51: 37–42.

    Google Scholar 

  • Zlotnick, I., Grant, D. P., and Batter-Hatton, D., 1972a, Encephalopathy in mice following inapparent Semliki Forest virus (SFV) infection, Br. J. Exp. Pathol. 53: 125–129.

    Google Scholar 

  • Zlotnick, I., Peacock, S., Grant, D. P., and Batter-Hatton, D., 1972b, The pathogenesis of Western equine encephalitis virus (WEE) in adult hamsters with special reference to the long and short term effects on the CNS of the attenuated clone 15 variant, Br. J. Exp. Pathol. 53: 59–77.

    Google Scholar 

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  1. Departments of Medicine and Neurology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205, USA

    Diane E. Griffin

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Griffin, D.E. (1986). Alphavirus Pathogenesis and Immunity. In: Schlesinger, S., Schlesinger, M.J. (eds) The Togaviridae and Flaviviridae. The Viruses. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-0785-4_8

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